The present invention relates to the manufacture, product, and method of using a highly crosslinked polystyrene N-halamine biocidal polymer. The biocidal polymer is produced under heterogeneous conditions due to its highly crosslinked nature, and in one instance can have pores.
While a variety of biocidal polymers (e.g., quaternary ammonium salts, phosphonium materials, halogenated sulfonamides, and biguanidesxe2x80x94see Trends Polym. Sci. 4:364 (1996)) have been synthesized and tested for biocidal activity, a relatively new class known as cyclic N-halamines has been shown to have far superior properties including biocidal efficacy, long-term stability, and rechargability once the efficacy has been lost. Such a material is poly-1,3-dichloro-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin which is an inexpensive derivative of poly-styrene, and which was first described in U.S. Pat. No. 5,490,983, now incorporated herein by reference. Subsequent disclosures of its biocidal properties for use in disinfecting applications for water filters have recently occurred [see Ind. Eng. Chem. Res. 33:168 (1994); Water Res. Bull. 32:793 (1996); Ind. Eng. Chem. Res. 34:4106 (1995); J. Virolog. Meth. 66:263 (1997); Trends in Polym. Sci. 4:364 (1996); Water Cond. and Pur. 39:96 (1997)]. The polymer is effective against a broad spectrum of pathogens including Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Klebsiella terrigena, Legionella pneumophila and rotavirus, among others, causing large log reductions in contact times of the order of a few seconds in water disinfectant applications. Furthermore, it is effective at pH values at least in the range 4.5 to 9.0 and at temperatures at least in the range 4xc2x0 C. to 37xc2x0 C., and it is capable of action even in water containing heavy chlorine demand caused by bioburden.
This biocidal polymer is insoluble in water and organic compounds and will thus not migrate in liquid media. It is stable for long periods of time in dry storage (a shelf life of at least one year at ambient temperature) and can be produced on an industrial scale. Furthermore, all evidence obtained to date suggests that the material is non-toxic and non-sensitizing to humans and animals upon contact.
A variety of microorganisms such as certain bacteria, fungi, and yeasts are capable of aiding the decomposition of bodily fluids such as urine and blood, or in the formation of biofilms, which produce undesirable odors in otherwise useful a commercial products. For example, bacteria such as Bacterium ammoniagenes and Proteus mirabilis are known to accentuate the decomposition of urea to form noxious ammonia gas through a urease enzyme catalysis mechanism (see for example U.S. Pat. No. 5,992,351). The same polymer mentioned above (poly-1,3-dichloro-5methyl-5-(4xe2x80x2-vinylphenyl)hydantoin) has been shown to be effective at inactivating Proteus mirabilis and thus minimizing the undesirable odor created by ammonia gas (U.S. patent application Ser. No. 09/685,963, herein incorporated by reference). Also, the polymer is insoluble in bodily fluids so as not to migrate to skin surfaces, rendering it useful in applications such as disposable diapers, incontinence pads, bandages, sanitary napkins, and pantiliners.
However, the composition of poly-1,3-dichloro-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin and use as a biocide for water-filter applications described in U.S. Pat. No. 5,490,983 and its use for odor control described in U.S. patent application Ser. No. 09/685,963 involved a form of the material which was a fine powder with a noticeable chlorine odor. In this form the material exhibited a tendency to cause excessive back-pressure in a water filtration application thereby slowing down flow rates, and the fine particles could potentially be aerosolized in an industrial setting causing concern for workers handling the material. Thus it was deemed necessary to find a method of creating the material as larger particles with less chlorine outgassing, while maintaining its biocidal efficacy.
The present invention relates to the manufacture, product and the use of novel highly crosslinked biocidal hydantoins in water and air filters and mixed with absorbent materials or as a coating for the prevention of noxious odors caused by the decomposition of organic materials contained in bodily fluids, on carpets and textile fibers, and in air filters or the like.
One embodiment of the invention is directed to a novel method of making highly crosslinked biocidal hydantoins from highly crosslinked polystyrene. A suitable amount of crosslinking is greater than 5%. In this form, the hydantoin is manufactured as particles rather than as a fine powder. In one embodiment the particle can include pores to increase the biocidal efficiency. Because of the highly crosslinked nature of the polymer, the reactions can proceed under heterogeneous conditions. In another embodiment the halogen loading can be controlled by either adjusting the pH or the halogen concentration during the halogenation step.
Another aspect of the invention is a novel highly crosslinked biocidal hydantoin. The hydantoin has polymeric chains having the following chemical formula: 
wherein,
X and Xxe2x80x2 are independently chlorine (Cl), bromine (Br), or hydrogen (H), provided that at least one of X and Xxe2x80x2 is Cl or Br; and
R1 is H or methyl (CH3). The amount of crosslinking is greater than 5%. In one embodiment of the invention, the hydantoin can be provided as a particle, wherein the particle shape is in the form of a bead. However, other embodiments can provide highly crosslinked hydantoin in any other shape. In one instance the bead is greater than 100 xcexcm or from about 100 xcexcm to about 1200 xcexcm. In another embodiment, the present invention can have pores, wherein the average of the pore size is greater than about 10 nm or from about 10 nm to 100 nm. The biocidal hydantoin made in accordance with the invention has novel highly crosslinked N-halamine polymers of poly-1,3-dihalo-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin, poly-1-halo-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin, and the alkali salt derivative of the monohalo species, and mixtures thereof, wherein the halogen can be either chlorine or bromine.
A biocidal particle made in accordance with the invention can be used in ways to provide numerous advantages. By providing a plurality of biocidal particles into a collection, such as a filter device, a suitable method of inactivating pathogenic microorganisms and viruses contained in water or air streams by contacting the water or air streams with the filters is provided. The biocidal particles, or beads, will prevent or minimize noxious odors by inactivating microorganisms upon contact which enhance, through catalytic enzymology, the decomposition of organic matter in bodily fluids to ammonia or other noxious materials. In one instance, the biocidal beads can be mixed with an absorbent material to form a mixture. The mixture is then introduced into any article that will contact bodily fluids and the mixture will inactivate halogen sensitive organisms. A biocidal bead made in accordance with the invention, prevents or minimizes noxious odors on air filters by inactivation of microorganisms such as those which cause mildew and molds, as well as those odors emanating from any liquid or aerosol which might contact the surface of the beads.
The present invention may be understood more readily by reference to the following detailed description of specific embodiments and the examples included therein.
As used herein, xe2x80x9cbiocidal polymerxe2x80x9d refers to the novel N-halamine polymers named poly-1,3-dihalo-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin, poly-1-halo-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin, and the alkali salt derivative of the monohalo species, and mixtures thereof, wherein the halogen can be either chlorine or bromine, although this is not meant to be limiting, as any other insoluble N-halamine polymer beads, porous or nonporous, could provide some degree of disinfection and odor-limiting capacity.
As used herein, xe2x80x9cbead,xe2x80x9d in singular or plural, refers to highly crosslinked polystyrene polymers or their reacted products. Beads can be of any size or shape, including spheres so as to resemble beads, but may also include irregularly shaped particles. xe2x80x9cBeadxe2x80x9d is used interchangeably with particle.
One aspect of the invention relates to the synthesis of the first intermediate poly-4-vinylacetophenone, useful in creating highly crosslinked halogenated hydantoins, using in one instance, porous beads of highly crosslinked poly-styrene as the starting material for the Friedel-Crafts acylation procedure. However, any other highly crosslinked poly-styrene polymer is suitable. Previously, the polystyrene employed in this reaction step contained minimal crosslinking such that it was soluble in Friedel-Crafts solvents such as carbon disulfide (U.S. Pat. No. 5,490,983). Since chemical reactions generally proceed best when all reactants are dissolved in a solvent to ensure maximum contact of the reactants, it was unexpected that the heterogeneous reaction of the highly crosslinked poly-styrene beads, which were insoluble in carbon disulfide, would react well with acetyl chloride under Friedel-Crafts conditions to produce beads in which the poly-4-vinylacetophenone was formed throughout the porous beads.
Another aspect of the invention relates to the heterogeneous reaction of the poly-4-vinylacetophenone beads with ammonium carbonate and (sodium or potassium) cyanide to produce beads having poly-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin throughout their porous structure useful in creating the highly crosslinked halogenated hydantoins. Previously (U.S. Pat. No. 5,490,983), the minimally crosslinked poly-4-vinylacetophenone was dissolved in a solvent such as an ethanol/water mix for this step which led to the formation of a product composed of a fine powder. Again, it was unexpected that the reaction could be made to proceed efficiently with the undissolved porous beads leading to a product having particle size similar to that of the highly crosslinked poly-styrene beads.
Another aspect of the invention relates to the heterogeneous halogenation of the poly-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin porous beads so as to produce either poly-1,3-dichloro-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin or poly-1,3-dibromo-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin or their monohalo derivatives (either protonated or as their alkali metal salts) or any mixture thereof, as beads, which are biocidal and maintain a particle size similar to the starting crosslinked poly-styrene beads.
Another aspect of the invention relates to control of the amount of biocidal halogen covalently bonded to the hydantoin rings on the beads by use of halogen reagent concentration control and/or of pH adjustments.
Another aspect of the invention relates to the use of poly-1,3-dichloro-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin and poly-1,3-dibromo-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin beads and their monohalo derivatives (either protonated or as their alkali metal salts) and mixtures thereof for inactivation of pathogenic microorganisms and viruses in water and air disinfection applications and for inactivation of organisms causing noxious odors.
Another aspect of the invention is directed to a highly crosslinked biocidal bead having the following chemical formula: 
wherein,
X, and Xxe2x80x2 are independently chlorine, bromine, hydrogen, provided that at least one of X and Xxe2x80x2 is chlorine or bromine, and R1 is hydrogen or methyl. The novelty of the biocidal bead is the starting compound used which is highly crosslinked polystyre having greater than 5% crosslinking. Such starting polystyrene polymers are well known to those in the art. However, their use in making the biocidal compounds of the present invention has heretofore been unknown. In one embodiment of a bead made according to the invention, the bead contains pores.
The present invention also relates to the use of a novel highly crosslinked, porous N-halamine biocidal polymer for the purpose of inactivating pathogenic microorganisms and viruses in water and air filtration applications, thereby rendering the water and/or air safe for human consumption. It also relates to the use of the same polymer for inactivating microorganisms such as bacteria, fungi, and yeasts which can cause noxious odors in commercial products such as disposable diapers, incontinence pads, bandages, sanitary napkins, pantiliners, sponges, mattress covers, shoe inserts, animal litter, carpets, fabrics, and air filters, thereby rendering the products free of noxious odors under normal use conditions.
The biocidal polymer beads to be used in this invention will be employed in one instance, in a cartridge filter application for water or air disinfection. The biocidal polymer beads can, for example, be mixed with an absorbent material wherein, the biocidal polymer weight percentage is about 0.1 to 5.0, or about 1.0, for applications involving bodily fluids such as disposable diapers, incontinence pads, bandages, sanitary napkins, pantiliners, mattress covers, shoe inserts, sponges, and animal litter. For air filters, coating techniques, or simple embedment of particles of the biocidal polymer into available filter material, a weight percentage of about 0.1 to 2.0, or about 0.5 to 1.0, can be employed. However, any amount of biocidal polymer made in accordance with this invention will realize beneficial biocidal activity.
The mechanism by which the biocidal polymer realizes biocidal activity is believed to be a result of surface contact of the organism with chlorine or bromine moieties covalently bound to the hydantoin functional groups of the polymer. The chlorine or bromine atoms are transferred to the cells of the microorganisms where they cause inactivation through a mechanism not completely understood, but probably involving oxidation of essential groups contained within the enzymes comprising the organisms.
It is contemplated that a wide variety of filtration devices, such as cartridges or sandwich cakes and the like can be used in conjunction with the biocidal polymer beads made according to the invention, from very large units in small water treatment plants and in the air-handling systems of large aircraft, hotels, and convention centers, to small filters as might be employed in household carafes and for faucets and portable devices for backpacking and military field use. It is further contemplated that a broad variety of absorbent and filler materials can be used in conjunction with the biocidal polymer to aid in preventing noxious odors. Suitably, such materials will enable the contact of the biocidal particles with the medium carrying the microorganisms, such as fluids, aerosol particles, and solid contaminants for sufficient periods of time such that the biocidal polymer particles can make surface contact with the odor-causing microorganisms, in addition to their usual absorptive functions. Such materials include, but are not limited to: swellable clays, zeolites, alumina, silica, cellulose, wood pulp, and super absorbent polymers. The odor control material could contain further adjuvants such as deodorants, fragrances, pigments, dyes, and mixtures of these for cosmetic purposes.
A marked advantage of the biocidal polymer beads of this invention over prior odor-controlling technology is that they are a much more effective biocide against pathogenic microorganisms encountered in medical applications such as S. aureus and P. aeruginosa than are commercial biocides such as the quaternary ammonium salts, so they can serve a dual function, i.e., inactivation of odor-causing microorganisms and disease-causing pathogens. For this reason they will have wide-spread use in hospital settings.
It should be understood that the practice of this invention applies to odors generated by both human and animal fluids as well as to airborne and waterborne organisms.
It should be emphasized that the biocidal polymer particle made in accordance with the invention can be created in a variety of sizes or shapes dependent upon the particle size or shape of the starting highly crosslinked poly-styrene material. In one instance the beads are porous to some degree allowing more efficient heterogeneous reactions to be performed upon them, although nonporous beads could be used also with concomitant lower biocidal efficacy. For the applications contemplated herein, the particle size of the biocidal polymer bead can be in the range of about 100 to 1200 xcexcm, or in the range of about 300 to 800xcexcm. This particle size provides adequate flow characteristics for microbiologically contaminated fluids and no risk of exposure of the respiratory systems of workers to fine aerosolized particles. These two factors are a marked improvement over the powder versions of poly-1,3-dichloro-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin or poly-1,3-dibromo-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin disclosed in U.S. Pat. No. 5,490,983 and use for odor control as described in U.S. patent application Ser. No. 09/685,963. For the applications contemplated herein the biocidal polymer beads can have pore sizes in the range of about 10 to 100 nm, or in the range of about 30 to 70 nm. A porous structure provides additional surface area for heterogeneous reaction steps, since the highly crosslinked beads are insoluble in organic solvents and water. Suitably, the degree of crosslinking of the starting poly-styrene material should be in the range of about 3 to 10 weight percent to insure hardness and lack of solubility, or about 5 to 8 weight percent, or even greater than 3% or greater than 5%. Non-limiting examples of highly crosslinked, porous poly-styrene beads which could be used in one aspect in accordance with this invention are obtained from Suqing Group (Jiangyin, Jiangsu, PRC) or from the Purolite Company (Philadelphia, Pa.).
In accordance with one aspect of the invention to make highly crosslinked biocidal hydantoin, a first step involves the suspension of highly crosslinked, porous poly-styrene beads in a Friedel-Crafts solvent, such as carbon disulfide, methylene chloride, an excess amount of acetyl chloride and the like and then reacted with acetyl chloride or acetic anhydride and the like in the presence of aluminum chloride, or gallium chloride and the like under reflux conditions. The isolated product, poly-4-vinylacetophenone beads, is purified by exposure to ice/HCl and then boiling water. The second reaction step in accordance with this invention includes reacting the pure poly-4-vinylacetophenone beads with potassium cyanide or sodium cyanide and ammonium carbonate or any source of gaseous ammonia in an ethanol/water mixture and the like solvent in a high pressure reactor suitable to contain the gaseous ammonia produced from the ammonium carbonate, which in one instance is run at about 85xc2x0 C., while the pressure is allowed to vary with the amount of ammonia produced. Thusly, producing poly-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin beads, which can be purified by exposure to boiling water rinses. The third reaction step in accordance with this invention includes the syntheses of the biocidal polymer beads (poly-1,3-dichloro-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin or poly-1,3-dibromo-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin) or their monohalo protonated or alkali metal salt derivatives by exposure of the poly-5-methyl-5-(4xe2x80x2-vinylphenyl)hydantoin beads to a source of free chlorine (e.g., gaseous chlorine, sodium hypochlorite, calcium hypochlorite, sodium dichloroisocyanurate, etc.) or free bromine (e.g., liquid bromine, sodium bromide/potassium peroxymonosulfate, etc.) in an aqueous base. If chlorine gas is used, the reactor should be chilled to about 10xc2x0 C. to minimize undesirable side reactions. Ambient temperature can be employed for the other sources of free halogen, and the reactions can be carried out in a reactor or in situ in a cartridge filter packed with the unhalogenated precursor. Optionally, the percent halogen on the polymer beads can be controlled by pH adjustments. For example, at pH 6-7 maximum halogenation is achieved; whereas, at pH near 12 a monohalogenated alkali metal salt is obtained. Intermediate pH""s (7-11) provide mixtures of dihalo and monohalo derivatives. The pH adjustments can be made using acids such as hydrochloric or acetic or bases such as sodium hydroxide or sodium carbonate. Higher free chlorine contents of greater than 14% chlorine by weight are suitable for water or air disinfection applications; whereas, the monohalo derivative or its alkali metal salt is adequate for odor control applications. On the other hand, bromine contents of greater than 34% are suitable for water disinfection applications. But because of outgassing, bromine, at these high concentrations, may be less suitable for air applications.